Early Intervention With Intranasal NPY Prevents Single Prolonged Stress-Triggered Impairments in Hypothalamus and Ventral Hippocampus in Male Rats

Abstract

Intranasal administration of neuropeptide Y (NPY) is a promising treatment strategy to reduce traumatic stress-induced neuropsychiatric symptoms of posttraumatic stress disorder (PTSD). We evaluated the potential of intranasal NPY to prevent dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, a core neuroendocrine feature of PTSD. Rats were exposed to single prolonged stress (SPS), a PTSD animal model, and infused intranasally with vehicle or NPY immediately after SPS stressors. After 7 days undisturbed, hypothalamus and hippocampus, 2 structures regulating the HPA axis activity, were examined for changes in glucocorticoid receptor (GR) and CRH expression. Plasma ACTH and corticosterone, and hypothalamic CRH mRNA, were significantly higher in the vehicle but not NPY-treated group, compared with unstressed controls. Although total GR levels were not altered in hypothalamus, a significant decrease of GR phosphorylated on Ser232 and increased FK506-binding protein 5 mRNA were observed with the vehicle but not in animals infused with intranasal NPY. In contrast, in the ventral hippocampus, only vehicle-treated animals demonstrated elevated GR protein expression and increased GR phosphorylation on Ser232, specifically in the nuclear fraction. Additionally, SPS-induced increase of CRH mRNA in the ventral hippocampus was accompanied by apparent decrease of CRH peptide particularly in the CA3 subfield, both prevented by NPY. The results show that early intervention with intranasal NPY can prevent traumatic stress-triggered dysregulation of the HPA axis likely by restoring HPA axis proper negative feedback inhibition via GR. Thus, intranasal NPY has a potential as a noninvasive therapy to prevent negative effects of traumatic stress.

Methodology and effects of repeated intranasal delivery of DNSP-11 in a rat model of Parkinson's disease

“…While the olfactory system is highly vascularized by facial arteries and/or through the transport by the lymphatic system [11, 12], it is likely that DNSP-11 would not be delivered systemically to the CNS due to a half-life of less than 12 minutes in rat plasma (data not shown). Collectively, these data show diffuse signal throughout the CNS at each time point, indicating a rapid delivery mechanism after intranasal administration to the CNS that suggesting a combination of either perivascular and/or perineural transport [33, 41, 42]. …”

Apoptotic endonuclease EndoG regulates alternative splicing of human telomerase catalytic subunit hTERT

“…Цитоплазму клеток получали согласно [13]. Клетки гомогенизировали на льду при помощи роторного гомогенизатора Ultra-Turrax T25 ("IKA", США) в 300 мкл буфера: 10 мМ HEPES ("Sigma", США), 10 мМ KCl ("Sigma"), 1,5 мM MgCl 2 ("Sigma"), 0,1 мM EGTA ("Sigma"), 0,3% NP-40, ингибитор протеаз (Protease Inhibitor Cocktail Tablets Complete, Mini, "Roche", Швейцария), pH 7,4, и центрифугировали в течение 3 мин при 2000 g и 4°С.…”

Intranasal gene delivery for treating Parkinson’s disease: overcoming the blood–brain barrier

“…NPY also mediates behavioral resilience to traumatic stress [137], neuroinflammation, neurogenesis, and neuroprotection in various models of CNS injury [138]. Intranasal NPY has emerged as a strong candidate for treatment of PTSD [137], reducing behavioral signs of stress in an animal model of PTSD and blunting the accompanying increases in plasma corticosterone and ACTH [27,139,140]. Early, acute interventions with intranasal NPY may be useful in mitigating the development of PTSD, making a gene therapy unnecessary.…”